Induction of posterior vitreous detachment (PVD) by non-enzymatic reagents targeting vitreous collagen liquefaction as well as vitreoretinal adhesion

• Published in: Scientific reports Vol. 10; no. 1; p. 8250
• Main Authors: Santra, Mithun, Sharma, Maryada, Katoch, Deeksha, Jain, Sahil, Saikia, Uma Nahar, Dogra, Mangat R., Luthra-Guptasarma, Manni
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19-05-2020; Nature Publishing Group
• Subjects: 631/80/79/1236; 692/308/153; 692/308/2778; Adhesion; Animals; Collagen; Collagen - administration & dosage; Collagen - chemistry; Collagen - genetics; Collagen - metabolism; Dehiscence; Humanities and Social Sciences; Humans; Integrins - genetics; Integrins - metabolism; Intravitreal Injections; Liquefaction; multidisciplinary; Peptides; Peptides - administration & dosage; Protein Domains; Rabbits; Reagents; Retina; Retina - drug effects; Retina - metabolism; RGD-containing peptides; Science; Science (multidisciplinary); Vitrectomy; Vitreous Body - drug effects; Vitreous Body - metabolism; Vitreous Detachment - drug therapy; Vitreous Detachment - genetics; Vitreous Detachment - metabolism; Vitreous Detachment - surgery
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-64931-3

Induction of posterior vitreous detachment (PVD) by pharmacologic vitreolysis has been largely attempted through the use of enzymatic reagents. Ocriplasmin has been the only FDA-approved clinical reagent so far. Several adverse effects of ocriplasmin have emerged, however, and the search for alternative PVD-inducing reagents continues. Since i) collagen forms an important structural component of the vitreous, and ii) strong vitreo-retinal adhesions exist between the cortical vitreous and the internal limiting membrane (ILM) of the retina, an effective PVD-inducing reagent would require both, vitreous liquefaction, and concurrent dehiscence of vitreoretinal adhesion, without being toxic to retinal cells. We designed a combination of two reagents to achieve these two objectives; a triple helix-destabilizing collagen binding domain (CBD), and a fusion of RGD (integrin-binding) tripeptide with CBD (RCBD) to facilitate separation of posterior cortical vitreous from retinal surface. Based on
in vitro
,
ex-vivo
, and
in vivo
experiments, we show that a combination of CBD and RCBD displays potential for safe pharmacologic vitreolysis. Our findings assume significance in light of the fact that synthetic RGD-containing peptides have already been used for inhibition of tumor cell invasion. Proteins such as variants of collagen binding domains could have extended therapeutic uses in the future.